Lewis trisaccharide

A. Lubineau and R. Lemoine, Regjoselective sulfation of galactose derivatives through the sttumylene procedure. New synthesis of the 3 -(>-sulfated Lewis trisaccharide. Tetrahedron Lett 35 8795 (1994). 

The FucT III transfers an L-fucose unit from GDP-fucose onto the 4-OH-group of a galactosylated N-acetylglucosamine in an a-niode to give the Lewis trisaccharide or the sialyl-Lewis tetrasaccharide, respectively (Fig. 13). 

The replacement of the N-acetyl group of the N-acetylglucosaniine unit is widely tolerated (Table 9). Especially striking is again the selective fucosylation of the glycuronamide derivatives (entries 11-15). Heterocyclic substituents on the acceptor apparently do not affect the enzyme either (entries 8-10). Nonnatural fucose donors are also recognized by FucT III and transferred in the expected way to form Lewis trisaccharides or sialyl-Lewis tetrasaccharides, respectively (see Fig. 14). 

Very recently, in a related approach, Norberg et al. presented the solid-phase enzymatic fucosylation of a disacchaiide acceptor linked to Sepharose via a disulfide linkage and a linker arm of 12 atoms with a loading of 5 to 10 pmol disaccharide ligand mL wet gel [18]. The sepharose-bound disaccharide 10 incubated with human milk a(l-3/4)fucosyltransferase and GDP-Fuc in fivefold excess was converted into the Sepharose-bound trisaccharide 11 in 68% glycosylation yield (Scheme 4). The Lewis trisaccharide derivative 12 could be released from the matrix, together with the starting disaccharide 13, by treatment with 2-mercaptoetha-nol, in 91% yield. 

Scheme 4. Solid-phase enzymatic synthesis of a Lewis trisaccharide by use of a disaccharide acceptor bound to Sepharose. Reagents i) cacodylate buffer pH 6.8, 5 mM MnCh, 0.05% NaN3, FT, GDP-Fuc (5 eq.) 68% ii) 2-mercaptoethanol, 1 h, 60 °C, 91%.

B, Lee RT, Lee YC, Huang SK Antigen coupled with 30 Lewis-x trisaccharides ehcits potent immune responses in mice. J Allergy Chn Immunol 2007 119 ... 

Regioselective glycosylatton of 38 with 2,3,4-tri-0-benzoyl-6-0-benzyl-a-D-galacto-pyranosyl bromide (37) and the following 3-O-ot-L-fucosylation of 39 gave the Lewis (Le ) trisaccharide donor 41, which was then coupled with 2-(triniethylsilyl)ethyl 0-(2,4,6-... 

Both Lewis Y and pseudo-Lewis Y are based on the Lewis X trisaccharide unit and differ only in the (a1-2)- or (a1 -3)-linkage of a second fucose to galactose, respectively. 

Jacquinet and Sinay [231] synthesised the trisaccharide (341) considered to be the possible determinant of the Lewis c (Lec) antigen. Condensation of (322) with compounds (343), both prepared via the allyl ethers (342), in the presence of bromide ion gave the trisaccharides (344) in 85 % yield in both cases. Deprotection of these gave (341). 

The Lewis a (Lea) blood-group trisaccharide determinant (345) first synthesised by Lemieux and co-workers [25] was also prepared by Sinay and co-workers [222] using the imidate procedure [232]. Condensation of the fucosyl imidate (321) with the disaccharide (346), prepared via the allyl ether (347), in the presence of toluene p-... 

The conformational behavior of a C/O-analogue (55) of the Lewis X trisaccharide has also been thoroughly analyzed by off-resonance-ROESY NMR... 

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